Clostridium Difficile Infection Testing Research Articles

Potential for Transmission of Spores by Patients Awaiting Laboratory Testing to Confirm Suspected Clostridium difficile Infection

In a prospective study of inpatients tested for Clostridium difficile infection (CDI), skin and environmental contamination were common at the time of the order for CDI testing, and there were often delays in completion of testing. Preemptive isolation of patients with suspected CDI may reduce the risk of transmission.

Impact of Change to Molecular Testing for Clostridium difficile Infection on Healthcare Facility–Associated Incidence Rates

Impact of Change to Molecular Testing for Clostridium difficile Infection on Healthcare Facility–Associated Incidence Rates

Low Rate of Clostridium Difficile Infection Testing in Patients With Newly Diagnosed Inflammatory Bowel Disease and Diarrhea

Clostridium difficile infection (CDI) has been reported in patients with inflammatory bowel disease (IBD) in the community and during hospitalization, and may occur in IBD without exposure to antibiotics. The rate of CDI in patients with and without IBD has increased over the last decade. CDI is associated with various adverse outcomes in IBD, including disease relapse, colectomy (in ulcerative colitis), hospitalization and mortality. Thus, testing for CDI in patients with diarrhea and IBD is considered standard of care. There is a lack of data regarding the prevalence of CDI in newly diagnosed IBD, and its effect on disease course. As a basis for future studies to determine the impact of CDI on the course of IBD, we sought to determine rate of CDI and CDI testing at diagnosis of IBD. Rhode Island patients diagnosed with IBD after January 2008 and within one year of diagnosis were eligible to enroll in the Ocean State Crohn's and Colitis Area Registry (OSCCAR), a prospective cohort started January 2008. Medically trained personnel confirmed diagnosis of IBD by chart review using standard criteria. All patients completed a questionnaire regarding symptoms at diagnosis. This included self-report of diarrhea (loose or watery bowel movements and/or increased frequency of stool) within 4 weeks before diagnosis of IBD. Trained data abstractors recorded occurrence of CDI toxin or PCR assay testing and results from medical records of the gastroenterologist and/or surgeon who reported a new diagnosis, or inpatient records if diagnosed during hospitalization. Among 338 patients enrolled from January 2008 to June 2011, 260 (76.9%) reported diarrhea. Of the 260 patients, results of CDI testing were recorded in diagnosing physicians' records for 120 patients (46.2%). CDI testing was not recorded or possibly not performed for the remaining 140 patients who presented with diarrhea. An additional 21 patients were tested for CDI but did not report having diarrhea or did not have a symptom inventory on record. Of the 141 patients tested for CDI, 74 were female; 65 were diagnosed with ulcerative colitis, 65 with Crohn's disease, and 11 patients had IBD undetermined. Seven (4.9%) of the 141 patients tested were positive for CDI (2.1% of all patients). Testing for CDI is lower than expected at diagnosis of IBD especially among patients who presented with diarrhea. Although the prevalence of CDI among tested patients is only 5%, low rate of testing and possible delayed diagnosis of CDI in newly diagnosed IBD may be a significant quality issue. A limitation of the study is that we are unable to determine whether CDI testing was done prior to specialty referral and thus we may underestimate the rate of CDI testing.

An Evaluation of Repeat Stool Testing for Clostridium difficile Infection by Polymerase Chain Reaction

To evaluate the yield of repeat stool polymerase chain reaction (PCR) testing in patients with suspected Clostridium difficile infection (CDI). CDI is a major challenge in health care due to its frequent occurrence and high associated costs. Enzyme immunoassay and PCR are commonly performed diagnostic tests for CDI. Our microbiology laboratory database was queried from January 1, 2008 to June 30, 2010 for all patients who underwent PCR stool testing for suspected CDI. Data collected included age, sex, number of stool tests performed within a 14-day period after the first test, and location of patient (inpatient vs. outpatient). Analyses were performed using JMP version 9.0.1. PCR testing was performed in 15,515 patients. The median age was 58.3 years (range, 10 d to 104.3 y) and 46.2% of patients were women. Repeat testing was infrequent; 87.3% of patients had testing performed only once in a 14-day period. Increased age, male sex, and inpatient location were predictors of repeat testing. The median time between an initial test and the first repeat test was 5 days. After an initial negative test, the percentage of patients having a subsequent positive test was low (2.7% in 7 d and 3.2% in 14 d). The percentage of repeat tests that was positive within 7 days (2.9%) was lower than the percentage that was positive from day 8 to day 14 (4.8%, P=0.05). Repeat testing for C. difficile has a low yield, and patients with an initial negative test should not routinely be retested.

Low Rate of Clostridium difficile Infection Testing in Patients with Newly Diagnosed Inflammatory Bowel Disease and Diarrhea

Purpose:Clostridium difficile infection (CDI) has been reported in patients with inflammatory bowel disease (IBD) in the community and during hospitalization, and may occur in IBD without exposure to antibiotics. The rate of CDI in patients with and without IBD has increased over the last decade. CDI is associated with various adverse outcomes in IBD, including disease relapse, colectomy (in ulcerative colitis), hospitalization and mortality. Thus, testing for CDI in patients with diarrhea and IBD is considered standard of care. Little data exist regarding the prevalence of CDI in newly diagnosed IBD, and its effect on disease course. As a basis for future studies to determine the impact of CDI on the course of IBD, we sought to determine rate of CDI and CDI testing at diagnosis of IBD. Methods: Rhode Island patients diagnosed with IBD after January 2008 and within one year of diagnosis were eligible to enroll in the Ocean State Crohn's and Colitis Area Registry (OSCCAR), a prospective cohort started January 2008. Medically trained personnel confirmed diagnosis of IBD by chart review using standard criteria. All patients completed a questionnaire regarding symptoms at diagnosis. This included self-report of diarrhea (loose or watery bowel movements and/or increased frequency of stool) within 4 weeks before diagnosis of IBD. Trained data abstractors recorded occurrence of CDI toxin or PCR assay testing and results from medical records of the gastroenterologist and/or surgeon who reported a new diagnosis, or inpatient records if diagnosed during hospitalization. Results: Among 338 patients enrolled from January 2008 to June 2011, 260 (76.9%) reported diarrhea. Of the 260 patients, results of CDI testing were recorded in diagnosing physicians' records for 120 patients (46.2%). CDI testing was not recorded or possibly not performed for the remaining 140 patients who presented with diarrhea. An additional 21 patients were tested for CDI but did not report having diarrhea or did not have a symptom inventory on record. Of the 141 patients tested for CDI, 74 were female; 65 were diagnosed with ulcerative colitis, 65 with Crohn's disease, and 11 patients had IBD undetermined. Seven (4.9%) of the 141 patients tested were positive for CDI (2.1% of all patients). Conclusion: Testing for CDI is lower than expected at diagnosis of IBD especially among patients who presented with diarrhea. Although the prevalence of CDI among tested patients is only ˜5%, low rate of testing and possible delayed diagnosis of CDI in newly diagnosed IBD may be a significant quality issue. A limitation of the study is that we are unable to determine whether CDI testing was done prior to specialty referral and thus we may underestimate the rate of CDI testing.

A Novel Use of Rectal Swab to Test for Clostridium difficile Infection by Real-Time PCR

Shakir, Faiz A MD1; Thompson, David MD2; Marlar, Richard MD3; Ali, Tauseef MD1 Author Information

Repeat stool testing for Clostridium difficile using enzyme immunoassay in patients with inflammatory bowel disease increases diagnostic yield

Background:The incidence and severity of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is increasing. CDI is diagnosed by toxin enzyme immunoassay (EIA) or real-time polymerase chain reaction (PCR) performed on stool samples. An earlier study evaluating EIA in IBD patients with CDI suggested that more than one stool sample be tested to increase diagnostic yield. We investigated whether repeat stool testing improves diagnostic accuracy for CDI in hospitalized IBD patients compared to hospitalized patients with CDI and no IBD.Methods:We performed retrospective data analysis from January 2005–May 2011 on 63,086 hospitalized patients who were tested for CDI using EIA or PCR. Of these, 2579 patients had IBD. Transition probabilities were calculated based on results from repeated tests.Results:Inclusive of all inpatients tested for CDI, 56,583 were tested using toxin EIA and 6503 were tested using PCR. In patients with no IBD, the first stool sample tested was positive in 90% and 94% with EIA and PCR respectively. In IBD patients tested using EIA, 101 were diagnosed with CDI. The first stool sample tested was positive in 81% of patients. Successive second and third stool samples yielded additional 14% and 5% CDI positive IBD patients.Conclusions:Approximately one in five IBD patients with CDI required repeat testing to yield a positive result with EIA. There are minimal diagnostic gains of repeat testing by EIA or PCR in patients without IBD. We recommend repeat stool testing for CDI when using EIA to increase diagnostic yield in IBD patients.

Policy development for Clostridium difficile

The Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI) was created at the height of the incidence of Clostridium difficile infection (CDI). This article describes the role of ARHAI in the evaluation of laboratory testing for CDI, a related consultation on the legal requirements for manufacturers of in vitro diagnostic medical devices, a CDI healthcare bundle and surveillance of CDI in children.

Evaluation of three enzyme immunoassays and a loop-mediated isothermal amplification test for the laboratory diagnosis of Clostridium difficile infection

The laboratory diagnosis of Clostridium difficile infection (CDI) consists of the detection of toxigenic Clostridium difficile, and/or its toxins A or B in stool preferably in a two-step algorithm. In a prospective study, we compared the performance of three toxin enzyme immunoassays (EIAs)-ImmunoCard Toxins A & B, Premier Toxins A & B and C. diff Quik Chek Complete, which combines a toxins test and a glutamate dehydrogenase (GDH) antigen EIA in one device -and the loop-mediated isothermal amplification assay Illumigene C. difficile. In total 986 stool samples were analyzed. Compared with toxigenic culture as the gold standard, sensitivities, specificities, PPV and NPV values of the toxin EIAs were 41.1-54.8%, 98.9-100%, 75.0-100% and 95.5-96.5% respectively, of the Illumigene assay 93.3%, 99.7%, 95.8% and 99.5%. Illumigene assays performed significantly better for non-014/020 PCR-ribotypes than for C. difficile isolates belonging to 014/020. Discrepant analysis of three culture-negative, but Illumigene-positive samples, revealed the presence of toxin genes using real-time PCRs. In addition to the GDH EIA (NPV of 99.8%), the performance of Illumigene allows this test to be introduced as a first screening test for CDI- or as a confirmation test for GDH -positive samples, although the initial invalid Illumigene result of 4.4% is a point of concern.

Comparison of Analytical and Clinical Performance of Three Methods for Detection of Clostridium difficile

Diagnostic laboratory testing for Clostridium difficile infection has undergone considerable and rapid evolution during the last decade. The ideal detection method(s), which should exhibit high analytical and clinical sensitivity and specificity, remains undefined. We sought to evaluate the analytical and clinical performance characteristics of three methods for the laboratory detection of C difficile. This study used 114 consecutive stool samples to compare three methods of C difficile detection: an enzyme immunoassay (EIA) for toxins A/B, a lateral flow membrane immunoassay for glutamate dehydrogenase (GDH), and a qualitative real-time polymerase chain reaction (PCR) assay. Medical records of all patients having ≥1 positive test result were reviewed to estimate the clinical likelihood of C difficile infection. Based upon laboratory result consensus values, analytical sensitivity was significantly higher for GDH (94%) and PCR (94%) assays than for toxin EIA (25%). Analytical specificity was significantly higher for PCR (100%) and EIA (100%) than for GDH assay (93%). In contrast, assay performance based upon clinical probability of C difficile infection suggested lower discriminatory power (ie, clinical specificity) of the more analytically sensitive methods. Higher rates of C difficile detection will be realized upon implementation of GDH assay and/or real-time PCR-based testing algorithms than by testing with EIA alone. Further study is required to elucidate potential downstream costs for higher detection rates.

654 Use of Rectal Swab to Test for Clostridium difficile Infection by Real Time-PCR

654 Use of Rectal Swab to Test for Clostridium difficile Infection by Real Time-PCR

Risk of secondary cases of Clostridium difficile infection among household contacts of index cases

We aimed to estimate the risk of secondary cases of Clostridium difficile infection (CDI) among household contacts of index cases. We reviewed all 2222 patients with confirmed CDI in a region of Quebec, Canada, during 1998-2009. Our laboratory serves a well-defined population for which it is the sole centre providing CDI testing, enabling us to calculate accurate population annual incidence rates of CDI. Cases with the same phone number were verified individually to determine whether they were indeed related. We considered as related two cases occurring in the same household within one year of each other. We estimated that 1061 spouses and 501 children (<25 years-old) lived in the same household as the index cases, of which respectively 5 and 3 developed CDI. Among spouses and children, the attack rate was 4.71/1000 and 5.99/1000 respectively, and the relative risk was 7.61 (95%CI: 5.77-9.78) and 90.6 (95%CI: 33.89-487.64) for the three months after the diagnosis in the index case. Although the relative risk of CDI among household contacts is somewhat increased for a few months, the absolute risk is too low to justify interventions, apart from avoiding unnecessary courses of antimicrobials.

An Evaluation of Repeat Polymerase Chain Reaction Stool Testing for Clostridium difficile Infection: 2011 ACG Presidential Poster

Purpose:Clostridium difficile infection (CDI) is a major health-care challenge with an increasing incidence and severity, worsening outcomes, and high associated costs. There have been considerable recent advances in infection control and treatment of CDI, and newer stool tests are available with increased sensitivity and specificity. It has been a common practice to repeat a stool test for CDI if the initial test is negative. In the current study, we evaluated our practice regarding the yield of repeat polymerase chain reaction (PCR) testing in patients with suspected CDI. Methods: The microbiology laboratory database at Mayo Clinic, Rochester, MN was queried for all patients who underwent PCR stool testing for suspected CDI from June 1, 2007 to May 31, 2010. Data collected included age, gender, number and timing of stool tests and location of patient (inpatient versus outpatient). Descriptive and multivariate regression analyses were done with JMP version 9.0.1. Results: PCR testing was performed in 18,629 patients in the three-year period. The median age of patients was 58.3 years (range 10 days to 104.3 years) and 46.2% were females. Repetitive testing was infrequent; 86.3% of patients had testing done only once in a 14-day period. On multivariate analysis, increased age, male sex, and in-patient location were predictors of repetitive testing. Patients with an initial negative test did not have an increased likelihood of repeat testing than those with an initial positive test (11.4% versus 10.2%, p=0.06). The mean time between an index test and a first repeat test was 3.5 days in a 7-day time period and 5.3 days in a 14-day time period. After an initial negative test, the chance of having a subsequent positive test was unlikely (2.4% in 7 days and 3.2% in 14 days). Conclusion: The yield of repeat stool testing for CDI by PCR is low, and patients with an initial negative stool test should not be re-tested for that bout of diarrhea unless clinical suspicion for CDI remains high.

Clostridium difficile infection in newly diagnosed pediatric patients with inflammatory bowel disease: Prevalence and risk factors

Epidemiological and microbiological data suggest that Clostridium difficile infection (CDI) plays a substantial role in the clinical initiation of inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and risk factors of CDI in newly diagnosed pediatric patients with IBD. The current investigation was a retrospective study. All patients newly diagnosed with IBD in the pediatric gastroenterology clinic in Warsaw between 2007 and 2010 were included in the present study. The patients were diagnosed according to Porto criteria and microbiology evaluation screening tests for CDI were conducted. Risk factors including prior hospitalization, use of antibiotics within 2 months of CDI detection, colonic involvement, and the duration of symptoms were evaluated. CDI diagnosis was based on a positive stool enzyme immunoassay. In the present study, 134 patients were evaluated (54 patients with Crohn's disease, and 80 with ulcerative colitis; 87% of the patients had colonic disease). The average age of the patients was 12.3 years, and the prevalence of CDI was 47% (95% confidence interval [CI], 38%-56%). Significant differences in the prevalence of CDI between patients with Crohn's disease and ulcerative colitis (P = 0.72; odds ratio [OR] = 1.187, 95% CI, 0.56-2.52) were not observed. The risk of CDI was associated with an increase in the age of the patient and the severity of the disease. The prevalence of CDI in newly diagnosed IBD patients was high and was independent of the type of disease.

Clostridium difficile infection in Tasmanian public hospitals 2006–2010

Abstract Objective To describe the current epidemiology of Clostridium difficile infection (CDI) in Tasmania Design, setting and participants Tasmania undertakes continuous surveillance for CDI at all public hospitals. Data on cases of CDI between 2006 and 2010 were examined. All positive tests occurring within 8 weeks of a previous case, and cases occurring in children less than 2 years old were excluded, consistent with national definitions. Only cases identified at public hospitals were included in the analysis Main outcome measures The rate of CDI in Tasmanian hospitals over the study period and the ability to demonstrate the effect of variances in surveillance definitions. Results A total of 357 cases of CDI were reported over the study period – a rate of 3.08 per 10 000 patient care days (95%CI 2.90–3.27) or 0.94 per 1000 patient separations (95%CI 0.91–0.98) for hospital-identified cases of CDI. Yearly rates for the period 2006 to 2010 were 2.3, 3.2, 2.8 and 3.9 per 10 000 patient care days, respectively. The overall trend was an increase in cases over the study period. The CDI rate from 2009–10 was significantly higher than that from 2008–09. Of the total cases reported,64% were healthcare-associated, healthcare-facility onset (HCAHFO), equating to a rate of 2.1 per 10 000 patient care days over the 4-year period. Conclusion The Tasmanian rate of HCA HFO is increasing, and appears to be greater than that reported by other Australian states, but is less than many northern hemisphere regions, where hypervirulent strains of C. difficile are causing increasing morbidity and mortality. It is difficult to compare reported rates of CDI nationally and internationally owing to inconsistencies in study duration, denominator selection, testing effort and testing methodology. This study demonstrates the need for national standards for CDI testing and reporting.

Diagnostic testing for Clostridium difficile: a comprehensive survey of laboratories in England

Recent studies have shown poor performance of commonly used toxin enzyme immunoassays (EIAs) for laboratory testing for Clostridium difficile infection (CDI). In 2009-2010, the UK Health Protection Agency and the European Society of Clinical Microbiology and Infectious Diseases stated that toxin EIA testing alone is suboptimal, and recommended a two-step testing protocol (i.e. screening with one method and confirming the results with another method). All acute English National Health Service trusts were surveyed to determine their testing methods and positivity rates using freedom of information requests. Replies were received from 168 of 170 trusts (99% response rate). Seventy percent of trusts were using a toxin EIA as a standalone testing method, with positive predictive values (PPVs) as low as 20% in some cases. The mean positivity rate decreased from 6.45% in 2008 to 4.47% in 2009, which will have a negative effect on the PPVs of these tests. The UK Department of Health publishes CDI rates as a measure of quality of care and good infection control practice. However, this may not provide valid comparisons because of the wide disparity between testing methods. The present study demonstrates wide variation in testing practices for CDI in England, and laboratories should reconsider their current testing strategies.

Clostridium difficile infection in patients with ulcerative colitis: Investigations of risk factors and efficacy of antibiotics for steroid refractory patients

The incidence of Clostridium difficile infection (CDI) has increased throughout the world and patients with ulcerative colitis (UC) are at a high risk for CDI. Potentially, CDI can exacerbate UC. Therefore, knowledge on the prevalence of CDI should contribute to better management of UC patients. The presence of toxin A antigen was defined as CDI, and the outcome of the test in patients with active UC during 2006-2009 was reviewed for identifying patients with CDI. Demographic data (disease profile, clinical response to medications and the need for colectomy) in UC patients with CDI were compared with the data from CDI free UC patients. Fifty-five of 137 patients (40.1%) were CDI positive. Univariate and multivariate analyses revealed that CDI was not associated with any demographic factor. Intensive antibiotic therapy spared five of 17 (29.4%) steroid refractory patients with CDI from steroids. CDI was not a predictor of colectomy although this could be an outcome of efficient eradication strategy. CDI was not associated with any demographic factor or colectomy rate. However, CDI eradication therapy allowed some refractory patients to withdraw from steroids. Patients with active UC benefit from regular CDI test and eradication treatment for CDI.

Laboratory Diagnosis of Clostridium difficile Infection

We read with interest the paper by Swindells et al. on the evaluation of diagnostic tests for Clostridium difficile infection recently published in this journal ([7][1]). We welcome this medium-sized study, which is timely and provides some clarity to the performance of assays for this difficult

Two-step glutamate dehydrogenase antigen real-time polymerase chain reaction assay for detection of toxigenic Clostridium difficile

Current diagnosis of Clostridium difficile infection (CDI) relies upon detection of toxins A/B in stool by enzyme immunoassay [EIA(A/B)]. This strategy is unsatisfactory because it has a low sensitivity resulting in significant false negatives. We investigated the performance of a two-step algorithm for diagnosis of CDI using detection of glutamate dehydrogenase (GDH). GDH-positive samples were tested for C. difficile toxin B gene (tcdB) by polymerase chain reaction (PCR). The performance of the two-step protocol was compared with toxin detection by the Meridian Premier EIA kit in 500 consecutive stool samples from patients with suspected CDI. The reference standard among samples that were positive by either EIA(A/B) or GDH testing was culture cytotoxin neutralisation (culture/CTN). Thirty-six (7%) of 500 samples were identified as true positives by culture/CTN. EIA(A/B) identified 14 of the positive specimens with 22 false negatives and two false positives. The two-step protocol identified 34 of the positive samples with two false positives and two false negatives. EIA(A/B) had a sensitivity of 39%, specificity of 99%, positive predictive value of 88% and negative predictive value of 95%. The two-step algorithm performed better, with corresponding values of 94%, 99%, 94% and 99% respectively. Screening for GDH before confirmation of positives by PCR is cheaper than screening all specimens by PCR and is an effective method for routine use. Current EIA(A/B) tests for CDI are of inadequate sensitivity and should be replaced; however, this may result in apparent changes in CDI rates that would need to be explained in national surveillance statistics.

Changing Clostridium difficile infection testing and treatment trends at a large tertiary care teaching hospital

To assess changes in testing and treatment trends of CDI at a time when the Clostridium difficile hypervirulent strain was first identified. A retrospective cohort study was performed. C. difficile cytotoxicity results were merged with pharmacy databases and changes in testing and treatment pattern over time were assessed. 6,613 tests for C. difficile were performed on 5,100 patients. Using least squares regression times series analysis, rates of testing increased by 0.63 +/- 0.31 tests per month (P = 0.05) although the number of positive tests did not increase significantly. Overall, metronidazole was the most commonly used drug (81.6%), followed by vancomycin (9.3%), rifaximin (8.4%), and nitazoxanide (0.70%). Use of rifaximin increased by 3.3 +/- 0.55 new prescriptions per month (Fig. 2; P < 0.01) while use of metronidazole increased by 5.0 +/- 2.8 new prescriptions per month and oral vancomycin increased by 0.4 +/- 0.7 new prescriptions per month; however these results were not statistically significant. For patients receiving rifaximin the drug was given as monotherapy (26.2%), in combination with oral vancomycin (24.2%), or in combination with metronidazole (49.7%). Increased rates of CDI testing and use of alternative therapies was observed at a time when the hypervirulent strain was first identified.